This application is a Competitive Revision, as described in Notice Number NOT-OD-058, entitled "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". The parent grant is R01DA017792-10, "Anxiolytic Effects and Abuse of BZ Receptor Ligands". The overall goal of the parent grant is to investigate the extent to which GABAA receptor subtypes are differentially involved in the anxiolytic effects, self-administration, and physical dependence associated with benzodiazepine (BZ) ligands, using relevant nonhuman primate models. The revised component of this application is to evaluate potential sex differences and menstrual cycle effects in BZ self-administration. In patient populations, women are associated with higher rates of BZ use and abuse, which we hypothesize to involve, in part, enhanced reinforcing effects of these ligands by sex hormones and their neuroactive steroid metabolites. Under the parent grant, reinforcing effects are evaluated using progressive-ratio schedules of i.v. drug self-administration, and we are requesting a revision to include experiments with both female and male monkeys. Identification of potential sex differences and menstrual cycle effects on the self-administration of BZ ligands will provide fundamental information for understanding gender-related differences in the abuse potential of these drugs that, in turn, should aid in developing safer and more broadly effective anti-anxiety medications. PUBLIC HEALTH RELEVANCE: Valium and related drugs, referred to as "benzodiazepines" are prescribed widely for the treatment of anxiety and sleep disorders, two of the most common psychiatric disorders in the U.S. Benzodiazepines are considered to be among the safest prescription drugs in modern medicine, but they unfortunately are also drugs of abuse, with higher prevalence in women than men. The aim of this revision to our parent grant is to uncover sex differences in the abuse potential of benzodiazepines, with the overall goal of developing safer drugs for treating anxiety and sleep disorders regardless of gender.